This research plan will continue the investigations initiated during the first three year budget period. Specifically, the work will examine the anatomy of the optic nerve head in cat, monkey and human eyes. Histologic examination of these specimens will include measurement of the cross-section diameter of individual axons, the cross-section area of nerve head micro-vasculature and the ratio of this area to that of nerve head fiber bundles, the three dimensional complexity of the glial and connective tissue trabecula within the lamina cribrosa and the cross section area and axonal interaction of intra-bundle glial tissue within the nerve head. The study will focus upon differences in this anatomy in regions of the nerve head with maximum versus minimum involvement of axon bundles by pressure-induced optic neuropathy. The extent of regional involvement by the pressure neuropathy will be characterized in one of three fashions depending upon the origin of the specimen examined. In cat eyes studied after an acute (four hour) pressure elevation, those regions of the nerve with pressure-induced axon damage will be identified by focal accomulation of tritium-labled protein at points of nerve transport interruption. In monkey eyes studied after a chronic (two to six months), laser-induced pressue elevation, the extent of regional axon loss will be quantitated by axon counts of remaining neurons. Finally, in human eyes, nerve head sectors known to be preferentially damaged by a pressure insult (supero-temporal and infero-temporal) will be compared to areas less often involved by the neuropathy (nasal). It is anticipated that clarification of the role local differences in optic nerve anatomy may play in defining preferential axon vulnerability to a pressure insult will increase our understanding of more basic mechanisms involved in pressure-induced axon damage.